WO2015063347A1 - Apparatus for controlling the flow rate in a microfluidic device - Google Patents

Apparatus for controlling the flow rate in a microfluidic device Download PDF

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Publication number
WO2015063347A1
WO2015063347A1 PCT/ES2013/070746 ES2013070746W WO2015063347A1 WO 2015063347 A1 WO2015063347 A1 WO 2015063347A1 ES 2013070746 W ES2013070746 W ES 2013070746W WO 2015063347 A1 WO2015063347 A1 WO 2015063347A1
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WO
WIPO (PCT)
Prior art keywords
microfluidic channel
microvalve
thermosensor
portable device
section
Prior art date
Application number
PCT/ES2013/070746
Other languages
Spanish (es)
French (fr)
Inventor
Aitor EZKERRA FERNÁNDEZ
Jaione ETXEBARRÍA ELEZGARAI
Jorge ELIZALDE GARCÍA
Original Assignee
Ikerlan, S. Coop.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ikerlan, S. Coop. filed Critical Ikerlan, S. Coop.
Priority to EP13803087.9A priority Critical patent/EP3078421A1/en
Priority to PCT/ES2013/070746 priority patent/WO2015063347A1/en
Publication of WO2015063347A1 publication Critical patent/WO2015063347A1/en

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Classifications

    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502738Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by integrated valves
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/08Regulating or influencing the flow resistance
    • B01L2400/082Active control of flow resistance, e.g. flow controllers

Definitions

  • the present invention is an apparatus for controlling the flow rate in a given section in a microfluidic device.
  • This apparatus is formed by a first interrelated product provided in the form of a portable device comprising microfluidic channels and a second interrelated product provided in the form of a control apparatus adapted to receive the first portable device.
  • the first portable device comprises at least one plate with at least one section of open microfluidic channel configured on the surface of the plate.
  • the same section of the microfluidic channel comprises a microvalve, either upstream of the thermosensor or downstream of the thermosensor, covered by a flexible sheet, which establishes a regulation of the flow in the stretch of microfluidic channel depending on the pressure exerted on the flexible sheet .
  • the invention allows the regulation of the flow in the section of the microfluidic channel by establishing a flow rate according to a setpoint value in the control apparatus with a closed loop regulation between the thermosensor signal and the microvalve.
  • microfluidic devices consist of a plate comprising cameras and microfluidic channels, also called microchannels, where experiments are carried out that give rise to results that would otherwise require laboratory tests. These devices are usually disposable.
  • small flow meters capable of measuring reduced flows are known.
  • they are capable of measuring very low flow rates they are not devices that can be incorporated into a microfluidic device and what is done is to arrange these devices either coupled to an input port or an output port, and always outside of the microfluidic device.
  • these micro flowmeters only measure the flow rate and do not provide a control that determines a certain flow rate value according to a setpoint value.
  • thermal sensors that measure the flow by incorporating thermal sensors. These thermal sensors are formed by a plurality of electrodes located inside the channel through which the fluid passes. Some of these electrodes are heated when they are fed by increasing the temperature of the fluid with which they are in contact. Other electrodes act as temperature sensors by measuring the temperature upstream and also downstream of the electrodes that provide heat. Depending on the flow rate, given the same heat input, the temperature increase measured in the flow will be greater or less. It is possible to establish a correlation between the temperature increase between the groups of electrodes intended for reading upstream and downstream and the flow through the electrodes determining the flow rate. However, in all cases the electrodes are located in the channel in order to be in contact with the fluid on which the flow is to be evaluated. This condition requires that known flowmeters be devices that must be incorporated in the specific place for which the microfluidic channel support has been designed together.
  • the present invention establishes a combination of sensor adapted to measure the flow rate in a section of microfluidic channel and a microvalve, placing the electrodes out of the channel.
  • This allows not only to integrate at a particular point of the microfluidic device, in particular at an intermediate point of the microfluidic path, without it having to be at an inlet or outlet port; and, in addition to establishing a control of said flow according to a preset setpoint.
  • a second technical advantage when the electrodes are placed in the control apparatus adapted to receive the microfluidic device, is the reduction of costs in the microfluidic portable device. If this portable microfluidic device is disposable, the electrodes are only necessary in the control apparatus and serve to carry out the measurements in a plurality of microfluidic devices instead of having to incorporate as many thermosensors as disposable devices.
  • the present invention is an apparatus for controlling the flow rate in a given section in a microfluidic device.
  • This apparatus is formed by a first interrelated product provided in the form of a portable device comprising microfluidic channels, typically a device called "Lab on a Chip", and a second interrelated product provided in the form of an adapted control apparatus. to receive the first portable device. It is this second control apparatus that acts on the first, the portable device, establishing a certain flow rate in a pre-established section of microfluidic channel.
  • the same control apparatus is capable of establishing a preset flow rate in different sections of the microfluidic channel of the portable device where these sections in which a certain flow rate is regulated can be intermediate sections between chambers, or between other elements and that are not necessarily in direct contact with the fluidic inlet and outlet of the microfluidic device.
  • the first interrelated product for flow control in a microfluidic device is provided in the form of a portable device and this comprises:
  • first conductive membrane thermally bonded to the support plate such that it covers the at least one section of microfluidic channel such that said section of microfluidic channel is closed by the first membrane.
  • the portable device that gives rise to the first interrelated product is mainly formed by a plate.
  • This board can contain cameras and channels inside, depending on the functions that you want the portable device.
  • it comprises an open channel section, that is, it is a channel with walls that are intended to guide the flow of a fluid sample but its section is not a closed path.
  • the open channel section is accessible from the outside before being covered by the first membrane.
  • This first membrane covers the open channel section extending along the outer surface of the plate containing the channel.
  • a particular way of applying this first membrane is by bonding it with adhesive to the plate.
  • the first membrane extends over the surface of the plate and in particular covers the open channel section resulting in a closed channel.
  • the first sheet that closes the open channel section is thermally conductive.
  • a region of the outer surface of the first sheet where the opposite side of said region is in contact with at least part of the section of the microfluidic channel is the region that will allow the reading of the flow through the microchannel section.
  • a thermosensor is arranged over this region. In an exemplary embodiment, this sensor has electrodes for generating heat. Heat is transmitted to the fluid because the first sheet is thermally conductive.
  • the thermosensor also has electrodes for reading the temperature upstream and downstream, with respect to the direction of the flow passing through the section of the microfluidic channel, of the electrodes that provide heat to the fluid.
  • the sheet is thermally conductive, it establishes a barrier to the passage of heat that can prevent the correct flow reading with the dimensions imposed on a microchannel.
  • the electrodes outside the microchannel leaving the membrane as an intermediate barrier between the electrodes and the fluid that passes through the microfluidic channel, it has been proven experimentally that the solution of incorporating the electrodes outside the sheet does not prevent the correct reading of the flow.
  • the electrodes that are placed on the surface region belong either to the portable device or to the machine in charge of carrying out the control over the portable device.
  • the electrodes can be deposited by sputtering, evaporation, screen printing, jet printing or a combination of any of them.
  • the placement of the first sheet only requires a good closing of the channels without the position requirements imposed by the electrodes being on this first sheet.
  • the second sheet does not have to cover the entire area of the first sheet so the placement of the second sheet containing the electrodes should only ensure correct positioning with respect to the region on the outer surface of the first conductive membrane intended to receive the electrodes
  • microvalve is configured according to an open cavity on the surface of the support plate
  • the open cavity has a microfluidic inlet and outlet, or the open cavity is covered by a flexible membrane such that it has a region of its outer surface adapted to receive a pressure actuator such that the pressure on said region causes deformation of the flexible membrane and the closure of the microvalve, where either the inlet or the outlet of said microvalve is in fluidic connection with the section of the microfluidic channel.
  • the flow regulation on the section of the microfluidic channel is carried out by acting on a micro valve that is in microfluidic communication with said section either upstream or downstream.
  • the microvalve is formed by an open cavity, interpreting as open a configuration equal to that of the open channel section, where the open cavity becomes closed because a flexible membrane covers it extending along the outer surface of the support plate where the cavity is located open
  • the regulation in closed loop between the flow measured in the thermosensor and the action on the microvalve establishes a flow through the section of microfluidic channel according to the set value of the closed loop.
  • the invention also has a second interrelated product provided in the form of a control apparatus.
  • This control apparatus is adapted to receive the portable device so that it is able to read the flow in the microfluidic channel section which has a region adapted to receive the thermosensor; and to act on the microvalve regulating the flow according to a preset setpoint.
  • This control apparatus comprises:
  • an actuator adapted to exert pressure on the region of the outer surface of the flexible membrane located covering the micro valve of the portable device once fixed on the fixing support and adapted to receive a pressure actuator
  • thermosensor adapted to come into contact with the region on the external surface of the first conductive membrane of the portable device once fixed on the fixing bracket; or, if the portable device already has a sensor, means for contacting said sensor when the portable device is fixed in the fixing bracket.
  • the control device receives the portable device in a fixing bracket.
  • the fixing support determines the position where either the region of the first membrane where the thermosensor is to be located or the electrodes of the thermosensor are located if the portable device has said thermosensor.
  • the thermosensor is arranged in the control apparatus in a position such that the thermosensor is in contact with the first thermally conductive membrane on the region adapted to receive the thermosensor.
  • the positioning that determines the fixing support allows the actuator intended to press on the microvalve to regulate its opening or closing is placed on the flexible membrane portion intended to admit actuator actuation by pressure.
  • thermosensor or comprising a signal input from the thermosensor where said central processing unit is adapted to determine the flow rate passing through the at least one section of microfluidic channel from the input signal, or comprising an output in connection with the actuator for the control of the microvalve,
  • central processing unit is configured in closed loop to regulate the flow through the micro valve to reach the setpoint value.
  • the central processing unit coordinates at least the flow reading by means of the thermosensor and the action on the actuator that establishes the degree of opening or closing of the microvalve according to a closed loop scheme.
  • This same central processing unit can manage a plurality of sensors and valves so that closed loop regulation can be carried out on a path containing a thermosensor, a valve, closing the rest of valves in such a way that the aforementioned path is established.
  • FIG 1 This figure shows a plan and elevation view of a microfluidic device according to a first embodiment comprising a channel on which a certain flow is to be imposed, a section of channel with a thermosensor for reading the flow rate , a section in bypass to increase the flow that is capable of regulating the microfluidic device; and, a microvalve.
  • the elevation view is shown immediately below the plan view with the membrane located slightly apart from the plate to distinguish both elements.
  • Figure 2a Figure 2a shows a first embodiment of a micro valve with a mechanical actuator.
  • Figure 2b shows a second embodiment of a micro valve with a pneumatic actuator.
  • Figure 3 shows a perspective of an embodiment of an open channel section, closed by a thermally conductive sheet on which the part of the electrodes that is active in the flow reading is shown.
  • Figure 4 is a diagram showing an exemplary embodiment of a control apparatus adapted to receive a portable device so that, once introduced into the control apparatus, it is possible to establish a certain flow rate in a stretch of microfluidic channel in said portable device.
  • Figure 5 shows a diagram of an exemplary embodiment of a portable device comprising a drive pump, either arranged integrated in the portable device, or external to said portable device, whose output is in fluidic communication with three sections, each of them comprising a sensor and a valve.
  • a drive pump either arranged integrated in the portable device, or external to said portable device, whose output is in fluidic communication with three sections, each of them comprising a sensor and a valve.
  • a flow regulation in any of the three branches of the portable device.
  • Figure 6 shows a diagram of an exemplary embodiment of a portable device comprising two possible inputs and a single output.
  • the fluid inlet is selected and, on this inlet, the flow regulation is carried out.
  • Figure 7 shows a diagram of an exemplary embodiment of a portable device comprising a single fluid inlet and two branches leading to each outlet.
  • the fluid outlet is selected and, on the branch that flows into said outlet, the flow regulation is carried out.
  • Figure 8 Figure 8 shows a graph in which three curves overlap.
  • the continuous line curve is a stepped function with the setpoint flow value imposed on a control device acting on a portable device.
  • the dashed curve is the flow response obtained before the imposition of the setpoint value in an embodiment of the invention, obtaining the reading by means of a thermosensor according to the invention arranged on the thermally conductive membrane.
  • the curve drawn in points is the response to the measurement flow using a commercial micro flow meter.
  • the present invention is an apparatus consisting of a first interrelated product and a second interrelated product.
  • the first interrelated product is the portable device (1) and the second interrelated product is the control device (2) that receives the portable device (1) to act on it (1) achieving that at least in a section of microfluidic channel ( 1.4) pass a preset flow as the setpoint value.
  • the plate (1.1) in which microfluidic channels and other cavities such as those giving rise to a microvalve (1.6) are distinguished; and, distanced from the plate (1.1), a membrane (1.2).
  • the membrane (1.2) is a thermally conductive sheet and is also flexible.
  • the same membrane (1.2) allows to establish the closure of the section of the microfluidic channel (1.4) on which the thermosensor (1.7.1) is arranged and also the closure of the microvalve cavity (1.6) with flexibility which allows the regulation of the degree of opening of said microvalve (1.6) by the deformation it suffers according to the pressure exerted on it.
  • the membrane (1.2) extends over one side of the plate (1.1) and is attached to it by means of an adhesive.
  • the flow rate reading in the narrow channel section (1.4) determines the flow rate in the channel section (1.5) bypass as the ratio of sections is known.
  • thermosensor (1.7.1) is formed by three electrode sections arranged on the membrane (1.2) as shown in detail in the embodiment shown in Figure 3.
  • a central electrode produces a pre-established amount of heat when It makes current flow through you. The heat it produces is transferred to the flow that passes through the channel through the membrane (1.2) since it is conductive to the passage of heat.
  • the electrodes arranged on the sides of this electrode intended to generate heat allow the temperature to be read before and after the heat is supplied. The temperature difference will be smaller the greater the flow that passes through the channel. The correlation between this temperature difference and the flow allows to measure the flow that passes through the microfluidic channel located under the thermosensor (1.7.1).
  • Figure 1 shows conductive tracks (1.7) located on the membrane (1.2) that establish the electrical communication between the supply and reading contacts, and the three electrodes acting as thermosensor (1.7.1) that are located on the microfluidic channel .
  • the conductive tracks (1.7) and in particular the electrodes acting as a thermosensor (1.7.1) are arranged on an adhesive sheet other than the membrane (1.2) and adheres on it in such a way that the electrodes acting as a thermosensor (1.7.1) they are properly positioned on the microfluidic channel in which the flow measurement is carried out.
  • the conductive tracks (1.7) and in particular the electrodes acting as thermosensor (1.7.1) are deposited by means of "sputtering", evaporation, screen printing, jet printing or a combination of any of them.
  • microvalve (1.6) is configured by means of a cavity (1.6.3) to which the inlet (1.6.1) arrives.
  • the outlet (1.6.2) is arranged at the bottom of the cavity (1.6.3) where in this embodiment the bottom shows a concavity.
  • the membrane (1.2) is pressed on its outer face by an actuator (3, 4) that exerts pressure.
  • the actuator is a bar that ends on a blunt surface and adapts to the concavity of the bottom of the cavity (1.6.3).
  • the actuator is formed by a chamber (4) that has a support (4.1) to achieve the seal when the membrane (1.2) is pressed externally; and, which has a conduit (4.2) for the injection of a gas, for example pressurized air.
  • the gas pressure is what causes the membrane to descend (1.2), deforming and causing the major or minor closure of the microvalve (1.6).
  • the regulation of the degree of opening of the microvalve (1.6) in this exemplary embodiment is carried out by managing the pressure introduced into the chamber (4) of the actuator.
  • FIG 4 schematically shows a portable device (1) that is inserted into the control apparatus (2). Once inserted and placed in the control device (2), the portable device (1) is positioned on the fixing support of the control device (2) where it (2) has at least one sensor module (S) that carries out the flow rate reading through the thermosensor (1.7.1).
  • the sensor module (S) has means of reading the value provided by the thermosensor (1.7.1) or, if there are several, of each of them.
  • It also has at least one actuator module (A), which acts on at least one microvalve (1.6) of those arranged in a section of microfluidic channel (1.3) to regulate the pre-established flow rate by entering a value in the control device (2) of setpoint. Likewise, if there are several microvalves (1.6), the actuator module (A) is capable of acting differently in each of them.
  • a central processing unit (CPU) receives the signal that comes from the at least one sensor module (S) and acts on the at least one actuator module (A) according to a closed loop regulation. That is, before a setpoint value, this setpoint value is compared with the value of the flow read by the sensor module (S). If the value of the flow rate read is greater than the setpoint value then the degree of actuator actuation (3, 4) that closes the microvalve (1.6) is increased. If, on the contrary, the value of the read flow rate is lower than the setpoint value then the degree of actuator actuation (3, 4) that closes the microvalve (1.6) is reduced to allow a greater flow rate.
  • Figure 5 shows a scheme of channels and microfluidic components according to an exemplary embodiment.
  • the portable device is powered by drive means (B).
  • the drive means are either integrated in the microfluidic device or are external to the portable device.
  • the output of the drive means (B) is in fluidic communication with three microfluidic channels in which, each of them, comprises a microvalve (1.6) and a thermosensor (1.7.1).
  • the control apparatus (2) for each of the microfluidic channels, performs a closed loop control by reading the flow rate on the microfluidic channel and acting on the micro valve (1.6) located in the same channel.
  • control unit processes in parallel a regulation on each of the channels so that it is possible to preset a different flow rate for each channel.
  • control unit processes a single closed loop control over one of the channels and, by means of the actuator module (A), keeps the other microvalves (1.6) closed.
  • the drive means can be a pump or a source of constant pressure flow.
  • Figure 6 shows a scheme of channels and microfluidic components according to another embodiment.
  • the portable device is powered by two different fluidic inlets.
  • Each of the fluidic inlets has a micro valve (1.6).
  • the output of each of the microvalves (1.6) is in communication with a single channel that has a sensor (1.7.1). This channel is the output.
  • This scheme can be generalized with a plurality of inputs each with a micro valve (1.6) that communicates with the sensor (1.7.1).
  • control apparatus (2) comprises a central processing unit (CPU) that is adapted to establish the closure of all microvalves (1.6) except one of them leaving a single possible path and therefore a single path. fluid inlet
  • CPU central processing unit
  • the same central processing unit (CPU) establishes the regulation of the channel that follows the only possible path by reading the flow in the sensor (1.7.1) and the action on the microvalve (1.6) that is not necessarily closed.
  • Figure 7 shows another embodiment in which there is a common fluid inlet to two channels.
  • the channel section corresponding to the common inlet has a main microvalve (1.6) and each channel that starts from this common inlet comprises a thermosensor (1.7.1) and a microvalve (1.6).
  • This scheme is generalizable by extending the number of two channels to a plurality of channels fed by the same input.
  • the control apparatus adapted to control the portable device according to this microfluidic scheme carries out a control that closes all the microvalves located in the individual microfluidic channels fed by the common input, except for a preset.
  • the open valve defines a single microfluidic path whose flow is determined with a closed loop control using the main microvalve (1.6) and the sensor (1.7.1) arranged in the channel that has its microvalve (1.6) open.
  • control section of the examples shown in figures 5, 6 and 7 may choose to change the valve configuration by defining another alternative path and therefore the combination of sensor (1.7.1) and microvalve (1.6) with the that carry out the control in closed loop.
  • the manufacture of electrodes that are deposited on the outer face of the membrane (1.2) allows sensing and flow control to be placed in any part of the microfluidic device or even in a plurality of places avoiding the design of input and output ports for coupling dedicated devices for the measurement or flow control.
  • the combination of a portable device and the device adapted to operate on said portable device is also object of this invention when the portable device is compatible in its configuration with the control device.
  • At least one experiment has been carried out where the capacity of response and flow regulation in a microchannel according to the invention is tested in the laboratory.
  • the experiment consists in establishing on the microchannel a flow determined by a setpoint value that follows an increasing step function.
  • Figure 8 shows in continuous line the increasing function according to staggered sections.
  • the response to the flow has been measured experimentally by two methods, a first method that makes use of the signal obtained in the thermosensor of the thermosensor of the portable device itself and a second method that makes use of a commercial flow meter arranged at the output of the built-in portable device how a device in series with the output of the microchannel.
  • Figure 8 shows in broken lines the response obtained according to the first method and in dotted lines the response measured by the second method.

Abstract

The invention relates to an apparatus for controlling the flow rate in a determined section of a microfluidic device. Said apparatus consists of a first interrelated product in the form of a portable device comprising microfluidic channels and a second interrelated product in the form of a control apparatus suitable for receiving the first portable device. The first portable device comprises at least one plate with at least one open microfluidic channel section embodied on the surface of the plate. On said microfluidic channel section, there is a thermally conductive strip which closes the open microfluidic channel, comprising a region in the outer surface which receives a heat sensor. The same microfluidic channel section comprises a microvalve, either upstream of the heat sensor or downstream of the heat sensor, covered by a flexible strip, which regulates the flow in the microfluidic channel section according to the pressure exerted on the flexible strip. The invention allows the regulation of the flow in the microfluidic channel section, establishing a flow rate according to a set value in the control apparatus with a closed-loop regulation between the signal of the heat sensor and the microvalve.

Description

APARATO PARA EL CONTROL DEL CAUDAL EN UN DISPOSITIVO MICROFLUÍDICO  APPLIANCE FOR FLOW CONTROL IN A MICROFLUID DEVICE
DESCRIPCIÓN  DESCRIPTION
OBJETO DE LA INVENCIÓN OBJECT OF THE INVENTION
La presente invención es un aparato para el control del caudal en un tramo determinado en un dispositivo microfluídico. Este aparato está formado por un primer producto interrelacionado provisto en la forma de un dispositivo portátil que comprende canales microfluídicos y un segundo producto interrelacionado provisto en la forma de un aparato de control adaptado para recibir el primer dispositivo portátil. The present invention is an apparatus for controlling the flow rate in a given section in a microfluidic device. This apparatus is formed by a first interrelated product provided in the form of a portable device comprising microfluidic channels and a second interrelated product provided in the form of a control apparatus adapted to receive the first portable device.
El primer dispositivo portátil comprende al menos una placa con al menos un tramo de canal microfluídico abierto configurado sobre la superficie de la placa. Sobre este tramo de canal microfluídico existe una lámina conductora térmicamente que cierra el canal microfluídico abierto comprendiendo una región en la superficie externa que admite un termosensor. El mismo tramo de canal microfluídico comprende una microválvula, o bien aguas arriba del termosensor o bien aguas abajo del termosensor, cubierta por una lámina flexible, que establece una regulación del flujo en el tramo de canal microfluídico dependiendo de la presión ejercida sobre la lámina flexible. The first portable device comprises at least one plate with at least one section of open microfluidic channel configured on the surface of the plate. On this stretch of microfluidic channel there is a thermally conductive sheet that closes the open microfluidic channel comprising a region on the outer surface that a thermosensor admits. The same section of the microfluidic channel comprises a microvalve, either upstream of the thermosensor or downstream of the thermosensor, covered by a flexible sheet, which establishes a regulation of the flow in the stretch of microfluidic channel depending on the pressure exerted on the flexible sheet .
La invención permite la regulación del flujo en el tramo de canal microfluídico estableciendo un caudal según un valor de consigna en el aparato de control con una regulación en lazo cerrado entre la señal del termosensor y la microválvula. The invention allows the regulation of the flow in the section of the microfluidic channel by establishing a flow rate according to a setpoint value in the control apparatus with a closed loop regulation between the thermosensor signal and the microvalve.
ANTECEDENTES DE LA INVENCIÓN BACKGROUND OF THE INVENTION
Uno de los campos de la técnica con un desarrollo más intenso en la actualidad es el de los dispositivos microfluídicos denominados en inglés "Lab on a Chip". Estos dispositivos están constituidos por una placa que comprende cámaras y canales microfluídicos, también denominados microcanales, en donde se llevan a cabo experimentos que dan lugar a resultados que de otra forma requerirían pruebas de laboratorio. Estos dispositivos son habitualmente desechables. One of the fields of technique with a more intense development today is that of microfluidic devices called "Lab on a Chip" in English. These devices consist of a plate comprising cameras and microfluidic channels, also called microchannels, where experiments are carried out that give rise to results that would otherwise require laboratory tests. These devices are usually disposable.
Algunos experimentos requieren la incorporación de reactivos, la medida de determinadas variables según la evolución de una muestra fluídica a lo largo de los canales microfluídicos; y en particular, existen experimentos que requieren establecer un determinado caudal. En estos últimos casos se conocen caudalímetros de dimensiones reducidas capaces de medir flujos reducidos. No obstante, aunque son capaces de medir caudales muy reducidos no son dispositivos que se puedan incorporar a un dispositivo microfluídico y lo que se hace es disponer estos dispositivos o bien acoplados a un puerto de entrada o bien a un puerto de salida, y siempre fuera del dispositivo microfluídico. No obstante, estos microcaudalímetros únicamente miden el caudal y no proveen de un control que determine un determinado valor del caudal según un valor de consigna. Some experiments require the incorporation of reagents, the measurement of certain variables according to the evolution of a fluid sample along the microfluidic channels; and in particular, there are experiments that require establishing a certain flow rate. In the latter cases, small flow meters capable of measuring reduced flows are known. However, although they are capable of measuring very low flow rates, they are not devices that can be incorporated into a microfluidic device and what is done is to arrange these devices either coupled to an input port or an output port, and always outside of the microfluidic device. However, these micro flowmeters only measure the flow rate and do not provide a control that determines a certain flow rate value according to a setpoint value.
Existen microcaudalímetros que miden el caudal incorporando sensores térmicos. Estos sensores térmicos están formados por una pluralidad de electrodos situados en el interior del canal por el que pasa el fluido. Unos de esos electrodos se calientan cuando son alimentados incrementando la temperatura del fluido con el que están en contacto. Otros electrodos actúan como sensores de temperatura midiendo la temperatura aguas arriba y también aguas abajo de los electrodos que aportan calor. Dependiendo del caudal de flujo, ante un mismo aporte de calor, el incremento de temperatura medido en el flujo será mayor o menor. Es posible establecer una correlación entre el incremento de temperatura entre los grupos de electrodos destinados a la lectura aguas arriba y aguas abajo y el flujo que pasa por los electrodos determinando el caudal. No obstante, en todos los casos los electrodos están situados en el canal para poder estar en contacto con el fluido sobre el que se quiere evaluar el caudal. Esta condición impone que los caudalímetros conocidos sean dispositivos que deben ser incorporados en el lugar específico para el que el soporte del canal microfluídico ha sido diseñado de forma conjunta. There are micro flowmeters that measure the flow by incorporating thermal sensors. These thermal sensors are formed by a plurality of electrodes located inside the channel through which the fluid passes. Some of these electrodes are heated when they are fed by increasing the temperature of the fluid with which they are in contact. Other electrodes act as temperature sensors by measuring the temperature upstream and also downstream of the electrodes that provide heat. Depending on the flow rate, given the same heat input, the temperature increase measured in the flow will be greater or less. It is possible to establish a correlation between the temperature increase between the groups of electrodes intended for reading upstream and downstream and the flow through the electrodes determining the flow rate. However, in all cases the electrodes are located in the channel in order to be in contact with the fluid on which the flow is to be evaluated. This condition requires that known flowmeters be devices that must be incorporated in the specific place for which the microfluidic channel support has been designed together.
La presente invención establece una combinación de sensor adaptado para medir el caudal en un tramo de canal microfluídico y una microválvula, situando los electrodos fuera del canal. Esto permite no solo integrar en un punto determinado del dispositivo microfluídico, en particular en un punto intermedio del camino microfluídico, sin que éste deba estar en un puerto de entrada o de salida; y, además establecer un control de dicho caudal según un valor de consigna preestablecido. Una segunda ventaja técnica, cuando los electrodos se sitúan en el aparato de control adaptado para recibir el dispositivo microfluídico, es la reducción de costes en el dispositivo portátil microfluídico. Si éste dispositivo portátil microfluídico es desechable, los electrodos solo son necesarios en el aparato de control y sirven para llevar a cabo las medidas en una pluralidad de dispositivos microfluídicos en lugar de tener que incorporar tantos termosensores como dispositivos desechables. The present invention establishes a combination of sensor adapted to measure the flow rate in a section of microfluidic channel and a microvalve, placing the electrodes out of the channel. This allows not only to integrate at a particular point of the microfluidic device, in particular at an intermediate point of the microfluidic path, without it having to be at an inlet or outlet port; and, in addition to establishing a control of said flow according to a preset setpoint. A second technical advantage, when the electrodes are placed in the control apparatus adapted to receive the microfluidic device, is the reduction of costs in the microfluidic portable device. If this portable microfluidic device is disposable, the electrodes are only necessary in the control apparatus and serve to carry out the measurements in a plurality of microfluidic devices instead of having to incorporate as many thermosensors as disposable devices.
DESCRIPCIÓN DE LA INVENCIÓN DESCRIPTION OF THE INVENTION
La presente invención es un aparato para el control del caudal en un tramo determinado en un dispositivo microfluídico. Este aparato está formado por un primer producto interrelacionado provisto en la forma de un dispositivo portátil que comprende canales microfluídicos, típicamente un dispositivo de los denominados "Lab on a Chip", y un segundo producto interrelacionado provisto en la forma de un aparato de control adaptado para recibir el primer dispositivo portátil. Es este segundo aparato de control el que actúa sobre el primero, el dispositivo portátil, estableciendo un determinado caudal en un tramo de canal microfluídico preestablecido. Según diversos ejemplos de realización, el mismo aparato de control es capaz de establecer un caudal preestablecido en distintos tramos de canal microfluídico del dispositivo portátil donde estos tramos en los que se regula un determinado caudal pueden ser tramos intermedios entre cámaras, o entre otros elementos y que no necesariamente están en contacto directo con la entrada y la salida fluídica del dispositivo microfluídico. The present invention is an apparatus for controlling the flow rate in a given section in a microfluidic device. This apparatus is formed by a first interrelated product provided in the form of a portable device comprising microfluidic channels, typically a device called "Lab on a Chip", and a second interrelated product provided in the form of an adapted control apparatus. to receive the first portable device. It is this second control apparatus that acts on the first, the portable device, establishing a certain flow rate in a pre-established section of microfluidic channel. According to various embodiments, the same control apparatus is capable of establishing a preset flow rate in different sections of the microfluidic channel of the portable device where these sections in which a certain flow rate is regulated can be intermediate sections between chambers, or between other elements and that are not necessarily in direct contact with the fluidic inlet and outlet of the microfluidic device.
El primer producto interrelacionado para el control del caudal en un dispositivo microfluídico, está provisto en la forma de un dispositivo portátil y éste comprende:The first interrelated product for flow control in a microfluidic device is provided in the form of a portable device and this comprises:
- una placa soporte con al menos un tramo de canal microfluídico abierto configurado sobre la superficie de la placa; - a support plate with at least one section of open microfluidic channel configured on the surface of the plate;
- una primera membrana conductora térmicamente unida a la placa soporte de tal modo que cubre el al menos un tramo de canal microfluídico de tal modo que dicho tramo de canal microfluídico queda cerrado por la primera membrana.  - a first conductive membrane thermally bonded to the support plate such that it covers the at least one section of microfluidic channel such that said section of microfluidic channel is closed by the first membrane.
El dispositivo portátil que da lugar al primer producto interrelacionado está formado principalmente por una placa. Esta placa puede contener en su interior cámaras y canales dependiendo de las funciones que se desea que cumpla el dispositivo portátil. En particular comprende un tramo de canal abierto, esto es, es un canal con paredes que están destinadas a guiar el flujo de una muestra fluídica pero su sección no es una trayectoria cerrada. El tramo de canal abierto es accesible desde el exterior antes de estar cubierto por la primera membrana. Esta primera membrana cubre el tramo de canal abierto extendiéndose por la superficie exterior de la placa que contiene el canal. Un modo particular de aplicar esta primera membrana es uniéndola mediante adhesivo a la placa. La primera membrana se extiende sobre la superficie de la placa y en particular cubre el tramo de canal abierto dando como resultado un canal cerrado. The portable device that gives rise to the first interrelated product is mainly formed by a plate. This board can contain cameras and channels inside, depending on the functions that you want the portable device. In particular, it comprises an open channel section, that is, it is a channel with walls that are intended to guide the flow of a fluid sample but its section is not a closed path. The open channel section is accessible from the outside before being covered by the first membrane. This first membrane covers the open channel section extending along the outer surface of the plate containing the channel. A particular way of applying this first membrane is by bonding it with adhesive to the plate. The first membrane extends over the surface of the plate and in particular covers the open channel section resulting in a closed channel.
- una región en la superficie externa de la primera membrana conductora, donde el lado opuesto a dicha región está en contacto con al menos parte del tramo del canal microfluídico, adaptada para recibir un termosensor de caudal. - a region on the outer surface of the first conductive membrane, where the side opposite to said region is in contact with at least part of the section of the microfluidic channel, adapted to receive a flow thermosensor.
La primera lámina que cierra el tramo de canal abierto es térmicamente conductora. Una región de la superficie externa de la primera lámina donde el lado opuesto a dicha región está en contacto con al menos parte del tramo del canal microfluídico es la región que va a permitir la lectura del caudal que pasa por el tramo de microcanal. Sobre esta región se dispone un termosensor. En un ejemplo de realización este sensor dispone de electrodos para generar calor. El calor es transmitido al fluido gracias a que la primera lámina es térmicamente conductora. El termosensor dispone también de electrodos para la lectura de la temperatura aguas arriba y aguas abajo, respecto de la dirección del flujo que pasa por el tramo del canal microfluídico, de los electrodos que aportan calor al fluido. Aunque la lámina es conductora térmicamente, establece una barrera al paso del calor que puede impedir la correcta lectura del caudal con las dimensiones impuestas en un microcanal. A pesar de haber situado los electrodos fuera del microcanal dejando la membrana como barrera intermedia entre los electrodos y el fluido que pasa por el canal microfluídico, se ha comprobado experimentalmente que la solución de incorporar los electrodos fuera de la lámina no impide la correcta lectura del caudal.  The first sheet that closes the open channel section is thermally conductive. A region of the outer surface of the first sheet where the opposite side of said region is in contact with at least part of the section of the microfluidic channel is the region that will allow the reading of the flow through the microchannel section. A thermosensor is arranged over this region. In an exemplary embodiment, this sensor has electrodes for generating heat. Heat is transmitted to the fluid because the first sheet is thermally conductive. The thermosensor also has electrodes for reading the temperature upstream and downstream, with respect to the direction of the flow passing through the section of the microfluidic channel, of the electrodes that provide heat to the fluid. Although the sheet is thermally conductive, it establishes a barrier to the passage of heat that can prevent the correct flow reading with the dimensions imposed on a microchannel. Despite having placed the electrodes outside the microchannel leaving the membrane as an intermediate barrier between the electrodes and the fluid that passes through the microfluidic channel, it has been proven experimentally that the solution of incorporating the electrodes outside the sheet does not prevent the correct reading of the flow.
Los electrodos que se sitúan sobre la región de la superficie, según distintos ejemplos de realización, o bien pertenecen al dispositivo portátil o bien a la máquina encargada de llevar a cabo el control sobre el dispositivo portátil. En el primer caso los electrodos pueden ser electrodos depositados mediante "sputtering", evaporación, serigrafía, impresión por chorro o una combinación de cualquiera de ellas. También pueden ser electrodos depositados sobre una segunda lámina, por ejemplo adhesiva, que se incorpora y se une a la superficie exterior de la primera lámina conductora térmicamente. En esta segunda solución la colocación de la primera lámina solo requiere un buen cierre de los canales sin los requerimientos de posición que impone el que los electrodos estén sobre esta primera lámina. La segunda lámina no tiene porqué cubrir la totalidad del área de la primera lámina por lo que la colocación de la segunda lámina conteniendo los electrodos solo debe asegurar un correcto posicionamiento respecto de la región en la superficie externa de la primera membrana conductora destinada a recibir los electrodos. The electrodes that are placed on the surface region, according to different embodiments, belong either to the portable device or to the machine in charge of carrying out the control over the portable device. In the first case, the electrodes can be deposited by sputtering, evaporation, screen printing, jet printing or a combination of any of them. Can also be electrodes deposited on a second sheet, for example adhesive, which is incorporated and bonded to the outer surface of the first thermally conductive sheet. In this second solution the placement of the first sheet only requires a good closing of the channels without the position requirements imposed by the electrodes being on this first sheet. The second sheet does not have to cover the entire area of the first sheet so the placement of the second sheet containing the electrodes should only ensure correct positioning with respect to the region on the outer surface of the first conductive membrane intended to receive the electrodes
- una microválvula donde: - a micro valve where:
o dicha microválvula está configurada según una cavidad abierta sobre la superficie de la placa soporte,  or said microvalve is configured according to an open cavity on the surface of the support plate,
o la cavidad abierta dispone de una entrada y una salida microfluídicas, o la cavidad abierta está cubierta por una membrana flexible de tal modo que dispone de una región de su superficie exterior adaptada para recibir un actuador por presión de tal modo que la presión sobre dicha región provoca la deformación de la membrana flexible y el cierre de la microválvula, donde o bien la entrada o bien la salida de dicha microválvula está en conexión fluídica con el tramo de canal microfluídico.  or the open cavity has a microfluidic inlet and outlet, or the open cavity is covered by a flexible membrane such that it has a region of its outer surface adapted to receive a pressure actuator such that the pressure on said region causes deformation of the flexible membrane and the closure of the microvalve, where either the inlet or the outlet of said microvalve is in fluidic connection with the section of the microfluidic channel.
La regulación del caudal sobre el tramo de canal microfluídico se lleva a cabo actuando sobre una microválvula que está en comunicación microfluídica con dicho tramo o bien aguas arriba o bien aguas abajo. La microválvula está formada por una cavidad abierta, interpretándose como abierta una configuración igual al del tramo de canal abierto, donde la cavidad abierta pasa a estar cerrada porque una membrana flexible la cubre extendiéndose por la superficie exterior de la placa soporte donde se encuentra la cavidad abierta.  The flow regulation on the section of the microfluidic channel is carried out by acting on a micro valve that is in microfluidic communication with said section either upstream or downstream. The microvalve is formed by an open cavity, interpreting as open a configuration equal to that of the open channel section, where the open cavity becomes closed because a flexible membrane covers it extending along the outer surface of the support plate where the cavity is located open
La acción de un actuador por presión sobre la superficie exterior de la membrana, dado que la membrana es elástica, provoca la deformación del tramo de membrana situado cubriendo la cavidad. La deformación provoca que la membrana invada el espacio de la cavidad reduciendo el espacio de la cámara que forma dicha cavidad. En particular el espacio por el que pasa el flujo de entrada, de salida, o ambos. Un modo particular de cerrar este espacio es porque la membrana llega a apoyar sobre la abertura que constituye la entrada o salida de la cavidad de la microválvula. La variación en la deformación de esta membrana da lugar a una mayor o menor restricción al paso del fluido. The action of an actuator by pressure on the outer surface of the membrane, since the membrane is elastic, causes deformation of the membrane section located covering the cavity. The deformation causes the membrane to invade the space of the cavity by reducing the space of the chamber that forms said cavity. In particular the space through which the flow of input, output, or both passes. A particular way of closing this space is because the membrane comes to rest on the opening that constitutes the inlet or outlet of the microvalve cavity. The variation in deformation of this membrane results in a greater or lesser restriction to the passage of fluid.
La regulación en lazo cerrado entre el caudal medido en el termosensor y la actuación sobre la microválvula establece un caudal de paso por el tramo de canal microfluídico de acuerdo al valor de consigna del lazo cerrado. The regulation in closed loop between the flow measured in the thermosensor and the action on the microvalve establishes a flow through the section of microfluidic channel according to the set value of the closed loop.
La invención también dispone de un segundo producto interrelacionado provisto en la forma de un aparato de control. Este aparato de control está adaptado para recibir al dispositivo portátil de modo que es capaz de leer el flujo en el tramo de canal microfluídico que dispone de una región adaptada para recibir el termosensor; y de actuar sobre la microválvula regulando el flujo conforme a un valor de consigna preestablecido. The invention also has a second interrelated product provided in the form of a control apparatus. This control apparatus is adapted to receive the portable device so that it is able to read the flow in the microfluidic channel section which has a region adapted to receive the thermosensor; and to act on the microvalve regulating the flow according to a preset setpoint.
Este aparato de control comprende: This control apparatus comprises:
- un soporte de fijación de un dispositivo portátil, - a support for fixing a portable device,
- un actuador adaptado para ejercer presión sobre la región de la superficie exterior de la membrana flexible situada cubriendo la microválvula del dispositivo portátil una vez fijado en el soporte de fijación y que está adaptada para recibir un actuador por presión,  - an actuator adapted to exert pressure on the region of the outer surface of the flexible membrane located covering the micro valve of the portable device once fixed on the fixing support and adapted to receive a pressure actuator,
- o bien un termosensor adaptado para entrar en contacto con la región en la superficie externa de la primera membrana conductora del dispositivo portátil una vez fijado en el soporte de fijación; o bien, si el dispositivo portátil ya dispone de sensor, medios para entrar en contacto con dicho sensor cuando el dispositivo portátil está f ijado en el soporte de fijación. - or a thermosensor adapted to come into contact with the region on the external surface of the first conductive membrane of the portable device once fixed on the fixing bracket; or, if the portable device already has a sensor, means for contacting said sensor when the portable device is fixed in the fixing bracket.
El aparato de control recibe el dispositivo portátil en un soporte de fijación. El soporte de fijación determina la posición donde se encuentran o bien la región de la primera membrana donde se ha de situar el termosensor o bien los electrodos del termosensor si el dispositivo portátil dispone de dicho termosensor. En el primer caso, el termosensor está dispuesto en el aparato de control en una posición tal que el termosensor queda en contacto con la primera membrana conductora térmicamente sobre la región adaptada para recibir el termosensor. Lo mismo sucede con las microválvulas. El posicionamiento que determina el soporte de fijación permite que el actuador destinado a presionar sobre la microválvula para regular su apertura o cierre se sitúe sobre la porción de membrana flexible destinada a admitir la actuación del actuador por presión. una unidad central de proceso: The control device receives the portable device in a fixing bracket. The fixing support determines the position where either the region of the first membrane where the thermosensor is to be located or the electrodes of the thermosensor are located if the portable device has said thermosensor. In the first case, the thermosensor is arranged in the control apparatus in a position such that the thermosensor is in contact with the first thermally conductive membrane on the region adapted to receive the thermosensor. The same goes for the microvalves. The positioning that determines the fixing support allows the actuator intended to press on the microvalve to regulate its opening or closing is placed on the flexible membrane portion intended to admit actuator actuation by pressure. a central processing unit:
o que comprende una entrada de señal del termosensor donde dicha unidad central de proceso está adaptada para determinar el caudal que pasa por el al menos un tramo de canal microfluídico a partir de la señal de entrada, o que comprende una salida en conexión con el actuador para el control de la microválvula,  or comprising a signal input from the thermosensor where said central processing unit is adapted to determine the flow rate passing through the at least one section of microfluidic channel from the input signal, or comprising an output in connection with the actuator for the control of the microvalve,
o que comprende una entrada para establecer un valor de consigna del caudal en el al menos un tramo de canal microfluídico; y,  or comprising an input to establish a setpoint value of the flow in the at least one section of microfluidic channel; Y,
o donde la unidad central de proceso está configurada en lazo cerrado para regular el caudal mediante la microválvula para alcanzar el valor de consigna.  or where the central processing unit is configured in closed loop to regulate the flow through the micro valve to reach the setpoint value.
La unidad central de proceso coordina al menos la lectura del caudal por medio del termosensor y la actuación sobre el actuador que establece el grado de apertura o cierre de la microválvula según un esquema de lazo cerrado. Esta misma unidad central de proceso, de acuerdo a diversos ejemplos de realización, puede gestionar una pluralidad de sensores y válvulas de forma que la regulación en lazo cerrado se puede llevar a cabo sobre un camino que contiene un termosensor, una válvula, cerrando el resto de válvulas de tal modo que se establezca el citado camino.  The central processing unit coordinates at least the flow reading by means of the thermosensor and the action on the actuator that establishes the degree of opening or closing of the microvalve according to a closed loop scheme. This same central processing unit, according to various embodiments, can manage a plurality of sensors and valves so that closed loop regulation can be carried out on a path containing a thermosensor, a valve, closing the rest of valves in such a way that the aforementioned path is established.
DESCRIPCIÓN DE LOS DIBUJOS DESCRIPTION OF THE DRAWINGS
Estas y otras características y ventajas de la invención, se pondrán más claramente de manifiesto a partir de la descripción detallada que sigue de una forma preferida de realización, dada únicamente a título de ejemplo ilustrativo y no limitativo, con referencia a las figuras que se acompañan. These and other features and advantages of the invention will become more clearly apparent from the detailed description that follows in a preferred embodiment, given only by way of illustrative and non-limiting example, with reference to the accompanying figures. .
Figura 1 En esta figura se muestra una vista en planta y en alzado de un dispositivo microfluídico según un primer ejemplo de realización que comprende un canal sobre el que se quiere imponer un determinado flujo, un tramo de canal con un termosensor para la lectura del caudal, un tramo en bypass para incrementar el flujo que es capaz de regular el dispositivo microfluídico; y, una microválvula. La vista en alzado se muestra inmediatamente debajo de la vista en planta con la membrana situada ligeramente distanciada de la placa para distinguir ambos elementos. Figura 2a La figura 2a muestra un primer ejemplo de realización de una microválvula con un actuador mecánico. Figure 1 This figure shows a plan and elevation view of a microfluidic device according to a first embodiment comprising a channel on which a certain flow is to be imposed, a section of channel with a thermosensor for reading the flow rate , a section in bypass to increase the flow that is capable of regulating the microfluidic device; and, a microvalve. The elevation view is shown immediately below the plan view with the membrane located slightly apart from the plate to distinguish both elements. Figure 2a Figure 2a shows a first embodiment of a micro valve with a mechanical actuator.
Figura 2b La figura 2b muestra un segundo ejemplo de realización de una microválvula con un actuador neumático. Figure 2b Figure 2b shows a second embodiment of a micro valve with a pneumatic actuator.
Figura 3 La figura 3 muestra una perspectiva de un ejemplo de realización de un tramo de canal abierto, cerrado mediante una lámina conductora térmicamente sobre la que se muestra la parte de los electrodos que es activa en la lectura del caudal. Figure 3 Figure 3 shows a perspective of an embodiment of an open channel section, closed by a thermally conductive sheet on which the part of the electrodes that is active in the flow reading is shown.
Figura 4 La figura 4 es un esquema que muestra un ejemplo de realización de un aparato de control adaptado para recibir un dispositivo portátil de modo que, una vez introducido en el aparato de control, es posible establecer un determinado caudal en un tramo de canal microfluídico en dicho dispositivo portátil. Figure 4 Figure 4 is a diagram showing an exemplary embodiment of a control apparatus adapted to receive a portable device so that, once introduced into the control apparatus, it is possible to establish a certain flow rate in a stretch of microfluidic channel in said portable device.
Figura 5 La figura 5 muestra un esquema de un ejemplo de realización de dispositivo portátil que comprende una bomba de impulsión, o bien dispuesta integrada en el dispositivo portátil, o bien externa a dicho dispositivo portátil, cuya salida está en comunicación fluídica con tres tramos, cada uno de ellos comprendiendo un sensor y una válvula. En este ejemplo de realización es posible llevar a cabo una regulación del flujo en cualquiera de las tres ramas del dispositivo portátil. Figure 5 Figure 5 shows a diagram of an exemplary embodiment of a portable device comprising a drive pump, either arranged integrated in the portable device, or external to said portable device, whose output is in fluidic communication with three sections, each of them comprising a sensor and a valve. In this exemplary embodiment it is possible to carry out a flow regulation in any of the three branches of the portable device.
Figura 6 La figura 6 muestra un esquema de un ejemplo de realización de dispositivo portátil que comprende dos posibles entradas y una única salida. En este ejemplo de realización se selecciona la entrada de fluido y, sobre esta entrada, se lleva a cabo la regulación del flujo. Figure 6 Figure 6 shows a diagram of an exemplary embodiment of a portable device comprising two possible inputs and a single output. In this embodiment, the fluid inlet is selected and, on this inlet, the flow regulation is carried out.
Figura 7 La figura 7 muestra un esquema de un ejemplo de realización de dispositivo portátil que comprende una única entrada de fluido y dos ramas que desembocan en sendas salidas. En este ejemplo de realización se selecciona la salida de fluido y, sobre la rama que desemboca en dicha salida se lleva a cabo la regulación del flujo. Figura 8 La figura 8 muestra una gráfica en la que se superponen tres curvas. La curva en trazo continuo es una función escalonada con el valor de flujo de consigna impuesto a un aparato de control actuando sobre un dispositivo portátil. La curva en trazo discontinuo es la respuesta en flujo obtenida ante la imposición del valor de consigna en un ejemplo de realización de la invención obteniendo la lectura mediante en termosensor según la invención dispuesto sobre la membrana conductora térmicamente. La curva trazada en puntos es la respuesta al flujo de medida haciendo uso de un microcaudalímetro comercial. Figure 7 Figure 7 shows a diagram of an exemplary embodiment of a portable device comprising a single fluid inlet and two branches leading to each outlet. In this exemplary embodiment, the fluid outlet is selected and, on the branch that flows into said outlet, the flow regulation is carried out. Figure 8 Figure 8 shows a graph in which three curves overlap. The continuous line curve is a stepped function with the setpoint flow value imposed on a control device acting on a portable device. The dashed curve is the flow response obtained before the imposition of the setpoint value in an embodiment of the invention, obtaining the reading by means of a thermosensor according to the invention arranged on the thermally conductive membrane. The curve drawn in points is the response to the measurement flow using a commercial micro flow meter.
EXPOSICIÓN DETALLADA DE LA INVENCIÓN DETAILED EXHIBITION OF THE INVENTION
La presente invención, de acuerdo al primer aspecto inventivo, es un aparato constituido por un primer producto interrelacionado y un segundo producto interrelacionado. El primer producto interrelacionado es el dispositivo portátil (1) y el segundo producto interrelacionado es el aparato de control (2) que recibe el dispositivo portátil (1) para actuar sobre él (1) consiguiendo que al menos en un tramo de canal microfluídico (1.4) pase un caudal preestablecido como valor de consigna. En la vista en alzado que se muestra en la parte inferior de la figura 1 se distingue la placa (1.1) en la que se encuentran canales microfluídicos y otras cavidades tales como las que dan lugar a una microválvula (1.6); y, distanciada de la placa (1.1), una membrana (1.2). En este ejemplo de realización la membrana (1.2) es una lámina conductora térmicamente y además es flexible. De este modo, la misma membrana (1.2) permite establecer el cierre del tramo de canal microfluídico (1.4) sobre el que se dispone el termosensor (1.7.1) y también el cierre de la cavidad de la microválvula (1.6) con la flexibilidad que permite la regulación del grado de apertura de dicha microválvula (1.6) por la deformación que sufre según la presión ejercida sobre ella. En este ejemplo de realización la membrana (1.2) se extiende sobre una cara de la placa (1.1) y queda unida a esta mediante un adhesivo. The present invention, according to the first inventive aspect, is an apparatus consisting of a first interrelated product and a second interrelated product. The first interrelated product is the portable device (1) and the second interrelated product is the control device (2) that receives the portable device (1) to act on it (1) achieving that at least in a section of microfluidic channel ( 1.4) pass a preset flow as the setpoint value. In the elevation view shown in the lower part of figure 1, the plate (1.1) in which microfluidic channels and other cavities such as those giving rise to a microvalve (1.6) are distinguished; and, distanced from the plate (1.1), a membrane (1.2). In this embodiment, the membrane (1.2) is a thermally conductive sheet and is also flexible. In this way, the same membrane (1.2) allows to establish the closure of the section of the microfluidic channel (1.4) on which the thermosensor (1.7.1) is arranged and also the closure of the microvalve cavity (1.6) with flexibility which allows the regulation of the degree of opening of said microvalve (1.6) by the deformation it suffers according to the pressure exerted on it. In this exemplary embodiment, the membrane (1.2) extends over one side of the plate (1.1) and is attached to it by means of an adhesive.
En la vista en planta que se muestra en la parte superior de la figura 1 se observa a la izquierda, siguiendo la orientación de la figura, una entrada a un canal microfluídico (1.3). Combinando la vista en planta y la vista en alzado se observa que esta entrada proviene de un tramo de canal dispuesto perpendicular a la placa de forma que desemboca en un canal abierto que discurre paralelo a la superficie y limitado por la membrana (1.2). A su vez, el canal abierto se amplía en sección dando lugar a dos tramos de canal, un primer tramo de canal (1.4) estrecho y un segundo tramo de canal ancho que está configurado en bypass (1.5). En este ejemplo de realización el flujo que se quiere regular es elevado. Es en el primer tramo de canal (1.4) estrecho en el que se dispone un termosensor (1.7.1) situado sobre la membrana (1.2). La lectura de caudal en el tramo de canal (1.4) estrecho determina el caudal en el tramo de canal (1.5) en bypass dado que la relación de secciones es conocida. Este modo particular de configurar un tramo de canal en bypass de sección mayor permite una lectura precisa mediante un termosensor ya que se sigue realizando la lectura en un canal microfluídico de pequeña sección, y permite el paso de caudales elevados para un dispositivo microfluídico. In the plan view shown in the upper part of figure 1, an entry to a microfluidic channel (1.3) is observed on the left, following the orientation of the figure. Combining the plan view and the elevation view, it is observed that This entrance comes from a section of channel arranged perpendicular to the plate so that it flows into an open channel that runs parallel to the surface and bounded by the membrane (1.2). In turn, the open channel is extended in section, giving rise to two sections of the channel, a first section of narrow channel (1.4) and a second section of wide channel that is configured bypass (1.5). In this embodiment, the flow to be regulated is high. It is in the first section of narrow channel (1.4) that a thermosensor (1.7.1) is placed on the membrane (1.2). The flow rate reading in the narrow channel section (1.4) determines the flow rate in the channel section (1.5) bypass as the ratio of sections is known. This particular way of configuring a section of channel in bypass of greater section allows an accurate reading by means of a thermosensor since the reading is still carried out in a microfluidic channel of small section, and allows the passage of high flows for a microfluidic device.
El termosensor (1.7.1) está formado por tres tramos de electrodo dispuestos sobre la membrana (1.2) tal y como se muestra en detalle en el ejemplo de realización mostrado en la figura 3. Un electrodo central produce una cantidad de calor preestablecida cuando se hace pasar corriente a través suyo. El calor que produce se transfiere al flujo que pasa por el canal a través de la membrana (1.2) ya que ésta es conductora al paso de calor. Los electrodos dispuestos a los lados de este electrodo destinado a generar calor permiten la lectura de la temperatura antes y después de aportar el calor. La diferencia de temperaturas será menor cuanto mayor sea el flujo que pasa por el canal. La correlación entre esta diferencia de temperaturas y el caudal permite medir el caudal que pasa por el canal microfluídico situado bajo el termosensor (1.7.1). The thermosensor (1.7.1) is formed by three electrode sections arranged on the membrane (1.2) as shown in detail in the embodiment shown in Figure 3. A central electrode produces a pre-established amount of heat when It makes current flow through you. The heat it produces is transferred to the flow that passes through the channel through the membrane (1.2) since it is conductive to the passage of heat. The electrodes arranged on the sides of this electrode intended to generate heat allow the temperature to be read before and after the heat is supplied. The temperature difference will be smaller the greater the flow that passes through the channel. The correlation between this temperature difference and the flow allows to measure the flow that passes through the microfluidic channel located under the thermosensor (1.7.1).
En la figura 1 se muestran pistas conductoras (1.7) situadas sobre la membrana (1.2) que establecen la comunicación eléctrica entre los contactos de alimentación y lectura, y los tres electrodos actuando como termosensor (1.7.1) que se sitúan sobre el canal microfluídico. Figure 1 shows conductive tracks (1.7) located on the membrane (1.2) that establish the electrical communication between the supply and reading contacts, and the three electrodes acting as thermosensor (1.7.1) that are located on the microfluidic channel .
Según un ejemplo de realización las pistas conductoras (1.7) y en particular los electrodos actuando como termosensor (1.7.1) se disponen sobre una lámina adhesiva distinta a la membrana (1.2) y se adhiere sobre esta de tal modo que los electrodos actuando como termosensor (1.7.1) quedan adecuadamente posicionados sobre el canal microfluídico en el que se lleva a cabo la medida del caudal. According to an embodiment, the conductive tracks (1.7) and in particular the electrodes acting as a thermosensor (1.7.1) are arranged on an adhesive sheet other than the membrane (1.2) and adheres on it in such a way that the electrodes acting as a thermosensor (1.7.1) they are properly positioned on the microfluidic channel in which the flow measurement is carried out.
Según otro ejemplo de realización las pistas conductoras (1.7) y en particular los electrodos actuando como termosensor (1.7.1) se depositan mediante "sputtering", evaporación, serigrafía, impresión por chorro o una combinación de cualquiera de ellas. According to another embodiment, the conductive tracks (1.7) and in particular the electrodes acting as thermosensor (1.7.1) are deposited by means of "sputtering", evaporation, screen printing, jet printing or a combination of any of them.
El flujo del tramo de canal microfluídico (1.4) y el flujo del bypass (1.5) convergen nuevamente en un canal que desemboca en la microválvula (1.6). Esta microválvula (1.6) está configurada mediante una cavidad (1.6.3) a la que llega la entrada (1.6.1). La salida (1.6.2) está dispuesta en el fondo de la cavidad (1.6.3) donde en este ejemplo de realización el fondo muestra una concavidad. La membrana (1.2) es presionada en su cara exterior por un actuador (3, 4) que ejerce presión. En el ejemplo de realización que se muestra en la figura 2a el actuador es una barra que termina en una superficie roma y que se adapta a la concavidad del fondo de la cavidad (1.6.3). Al descender, siempre según la orientación mostrada en la figura, penetrando en la cavidad (1.6.3) fuerza la deformación de la membrana (1.2) que también desciende reduciendo el espacio que permite el paso del fluido a través de la salida (1.6.2). En el caso límite la membrana (1.2) apoya completamente sobre la concavidad estableciendo el cierre completo. En esta misma figura se muestra una primera posición identificada como i) donde el actuador (3) no presiona sobre la membrana (1.2) dejando la microválvula (1.6) abierta, una segunda posición intermedia identificada como ii) donde el actuador (3) presiona sobre la membrana (1.2) dejando la microválvula (1.6) parcialmente abierta; y, una tercera posición identificada como iii) donde el actuador (3) presiona sobre la membrana (1.2) dejando la microválvula (1.6) cerrada. En el ejemplo de realización mostrado en la figura 2b el actuador está formado por una cámara (4) que dispone de un apoyo (4.1) para conseguir el cierre estanco cuando presiona la membrana (1.2) exteriormente; y, que dispone de un conducto (4.2) para la inyección de un gas, por ejemplo aire a presión. La presión del gas es la que provoca el descenso de la membrana (1.2) deformándose y provocando el mayor o menor cierre de la microválvula (1.6). La regulación del grado de apertura de la microválvula (1.6) en este ejemplo de realización se lleva a cabo gestionando la presión introducida en la cámara (4) del actuador. The flow of the microfluidic channel section (1.4) and the bypass flow (1.5) converge again in a channel that flows into the microvalve (1.6). This microvalve (1.6) is configured by means of a cavity (1.6.3) to which the inlet (1.6.1) arrives. The outlet (1.6.2) is arranged at the bottom of the cavity (1.6.3) where in this embodiment the bottom shows a concavity. The membrane (1.2) is pressed on its outer face by an actuator (3, 4) that exerts pressure. In the exemplary embodiment shown in Figure 2a, the actuator is a bar that ends on a blunt surface and adapts to the concavity of the bottom of the cavity (1.6.3). When descending, always according to the orientation shown in the figure, penetrating the cavity (1.6.3) forces the deformation of the membrane (1.2) that also descends reducing the space that allows the passage of the fluid through the outlet (1.6. 2). In the limit case, the membrane (1.2) rests completely on the concavity, establishing the complete closure. This same figure shows a first position identified as i) where the actuator (3) does not press on the membrane (1.2) leaving the microvalve (1.6) open, a second intermediate position identified as ii) where the actuator (3) presses on the membrane (1.2) leaving the microvalve (1.6) partially open; and, a third position identified as iii) where the actuator (3) presses on the membrane (1.2) leaving the microvalve (1.6) closed. In the exemplary embodiment shown in Figure 2b, the actuator is formed by a chamber (4) that has a support (4.1) to achieve the seal when the membrane (1.2) is pressed externally; and, which has a conduit (4.2) for the injection of a gas, for example pressurized air. The gas pressure is what causes the membrane to descend (1.2), deforming and causing the major or minor closure of the microvalve (1.6). The regulation of the degree of opening of the microvalve (1.6) in this exemplary embodiment is carried out by managing the pressure introduced into the chamber (4) of the actuator.
La figura 4 muestra esquemáticamente un dispositivo portátil (1) que se introduce en el aparato de control (2). Una vez introducido y situado en el aparato de control (2), el dispositivo portátil (1) queda posicionado sobre el soporte de fijación del aparato de control (2) donde éste (2) dispone de al menos un módulo sensor (S) que lleva a cabo la lectura del caudal a través del termosensor (1.7.1). El módulo sensor (S) dispone de medios de lectura del valor aportado por el termosensor (1.7.1) o, si hay varios, de cada uno de ellos. Figure 4 schematically shows a portable device (1) that is inserted into the control apparatus (2). Once inserted and placed in the control device (2), the portable device (1) is positioned on the fixing support of the control device (2) where it (2) has at least one sensor module (S) that carries out the flow rate reading through the thermosensor (1.7.1). The sensor module (S) has means of reading the value provided by the thermosensor (1.7.1) or, if there are several, of each of them.
Igualmente dispone de al menos un módulo actuador (A), que actúa al menos sobre una microválvula (1.6) de las dispuestas en un tramo de canal microfluídico (1.3) para regular el caudal preestablecido introduciendo en el aparato de control (2) un valor de consigna. Igualmente, si hay varias microválvulas (1.6), el módulo actuador (A) es capaz de actuar de forma diferenciada en cada una de ellas. It also has at least one actuator module (A), which acts on at least one microvalve (1.6) of those arranged in a section of microfluidic channel (1.3) to regulate the pre-established flow rate by entering a value in the control device (2) of setpoint. Likewise, if there are several microvalves (1.6), the actuator module (A) is capable of acting differently in each of them.
Una unidad central de proceso (CPU), recibe la señal que proviene del al menos un módulo sensor (S) y actúa sobre el al menos módulo actuador (A) de acuerdo a una regulación en lazo cerrado. Esto es, ante un valor de consigna, este valor de consigna se compara con el valor del flujo leído mediante el módulo sensor (S). Si el valor del caudal leído es superior al valor de consigna entonces se incrementa el grado de actuación del actuador (3, 4) que cierra la microválvula (1.6). Si por el contrario, el valor del caudal leído es inferior al valor de consigna entonces se reduce el grado de actuación del actuador (3, 4) que cierra la microválvula (1.6) para dejar un mayor paso de caudal. A central processing unit (CPU) receives the signal that comes from the at least one sensor module (S) and acts on the at least one actuator module (A) according to a closed loop regulation. That is, before a setpoint value, this setpoint value is compared with the value of the flow read by the sensor module (S). If the value of the flow rate read is greater than the setpoint value then the degree of actuator actuation (3, 4) that closes the microvalve (1.6) is increased. If, on the contrary, the value of the read flow rate is lower than the setpoint value then the degree of actuator actuation (3, 4) that closes the microvalve (1.6) is reduced to allow a greater flow rate.
La figura 5 muestra un esquema de canales y componentes microfluídicos según un ejemplo de realización. En este ejemplo de realización el dispositivo portátil es alimentado por unos medios de impulsión (B). Los medios de impulsión o bien están integrados en el dispositivo microfluídico o bien son externos al dispositivo portátil. La salida de los medios de impulsión (B) está en comunicación fluídica con tres canales microfluídicos en los que, cada uno de ellos, comprende una microválvula (1.6) y un termosensor (1.7.1). El aparato de control (2), para cada uno de los canales microfluídicos, lleva a cabo un control en lazo cerrado mediante la lectura del caudal sobre el canal microfluídico y actuando sobre la microválvula (1.6) situada en el mismo canal. Figure 5 shows a scheme of channels and microfluidic components according to an exemplary embodiment. In this exemplary embodiment, the portable device is powered by drive means (B). The drive means are either integrated in the microfluidic device or are external to the portable device. The output of the drive means (B) is in fluidic communication with three microfluidic channels in which, each of them, comprises a microvalve (1.6) and a thermosensor (1.7.1). The control apparatus (2), for each of the microfluidic channels, performs a closed loop control by reading the flow rate on the microfluidic channel and acting on the micro valve (1.6) located in the same channel.
Según un ejemplo de realización, la unidad de control (CPU) procesa en paralelo una regulación sobre cada uno de los canales de modo que es posible preestablecer de forma diferenciada un caudal distinto para cada canal. According to an exemplary embodiment, the control unit (CPU) processes in parallel a regulation on each of the channels so that it is possible to preset a different flow rate for each channel.
Según otro ejemplo de realización, la unidad de control (CPU) procesa un único control en lazo cerrado sobre uno de los canales y, mediante el módulo actuador (A), mantiene cerradas las otras microválvulas (1.6). According to another embodiment, the control unit (CPU) processes a single closed loop control over one of the channels and, by means of the actuator module (A), keeps the other microvalves (1.6) closed.
En cualquiera de los casos los medios de impulsión puede ser una bomba o bien una fuente de flujo a presión constante. In either case the drive means can be a pump or a source of constant pressure flow.
En la figura 6 se muestra un esquema de canales y componentes microfluídicos según otro ejemplo de realización. En este ejemplo de realización el dispositivo portátil es alimentado por dos entradas fluídicas distintas. Cada una de las entradas fluídicas dispone de una microválvula (1.6). La salida de cada una de las microválvulas (1.6) está en comunicación con un único canal que dispone de un sensor (1.7.1). Este canal es el de salida. Figure 6 shows a scheme of channels and microfluidic components according to another embodiment. In this exemplary embodiment, the portable device is powered by two different fluidic inlets. Each of the fluidic inlets has a micro valve (1.6). The output of each of the microvalves (1.6) is in communication with a single channel that has a sensor (1.7.1). This channel is the output.
Este esquema se puede generalizar con una pluralidad de entradas cada una de ellas con una microválvula (1.6) que comunica con el sensor (1.7.1). This scheme can be generalized with a plurality of inputs each with a micro valve (1.6) that communicates with the sensor (1.7.1).
En este ejemplo de realización el aparato de control (2) comprende una unidad central de proceso (CPU) que está adaptada para establecer el cierre de todas las microválvulas (1.6) salvo una de ellas dejando un único camino posible y por lo tanto una única entrada de fluido. La misma unidad central de proceso (CPU) establece la regulación del canal que sigue el único camino posible mediante la lectura del caudal en el sensor (1.7.1) y la actuación sobre la microválvula (1.6) que no necesariamente está cerrada. In this exemplary embodiment, the control apparatus (2) comprises a central processing unit (CPU) that is adapted to establish the closure of all microvalves (1.6) except one of them leaving a single possible path and therefore a single path. fluid inlet The same central processing unit (CPU) establishes the regulation of the channel that follows the only possible path by reading the flow in the sensor (1.7.1) and the action on the microvalve (1.6) that is not necessarily closed.
La figura 7 muestra otro ejemplo de realización en el que existe una entrada de fluido común a dos canales. El tramo de canal que corresponde a la entrada común dispone de una microválvula (1.6) principal y cada canal que parte de esta entrada común comprende un termosensor (1.7.1) y una microválvula (1.6). Este esquema es generalizable extendiendo el número de dos canales a una pluralidad de canales alimentados por la misma entrada. Figure 7 shows another embodiment in which there is a common fluid inlet to two channels. The channel section corresponding to the common inlet has a main microvalve (1.6) and each channel that starts from this common inlet comprises a thermosensor (1.7.1) and a microvalve (1.6). This scheme is generalizable by extending the number of two channels to a plurality of channels fed by the same input.
El aparato de control adaptado para controlar el dispositivo portátil conforme a este esquema microfluídico lleva a cabo un control que cierra todas las microválvulas situadas en los canales microfluídicos individuales alimentados por la entrada común, salvo una preestablecida. La válvula abierta define un único camino microfluídico cuyo caudal se determina con un control en lazo cerrado haciendo uso de la microválvula (1.6) principal y del sensor (1.7.1) dispuesto en el canal que tiene su microválvula (1.6) abierta. The control apparatus adapted to control the portable device according to this microfluidic scheme carries out a control that closes all the microvalves located in the individual microfluidic channels fed by the common input, except for a preset. The open valve defines a single microfluidic path whose flow is determined with a closed loop control using the main microvalve (1.6) and the sensor (1.7.1) arranged in the channel that has its microvalve (1.6) open.
El apartado de control de los ejemplos que se muestran en las figuras 5, 6 y 7 pueden optar por cambiar la configuración de válvulas definiendo otro camino alternativo y por lo tanto la combinación de sensor (1.7.1) y microválvula (1.6) con la que llevan a cabo el control en lazo cerrado. The control section of the examples shown in figures 5, 6 and 7 may choose to change the valve configuration by defining another alternative path and therefore the combination of sensor (1.7.1) and microvalve (1.6) with the that carry out the control in closed loop.
La fabricación de electrodos que se depositan en la cara exterior de la membrana (1.2) permite situar el sensado y control del flujo en cualquier parte del dispositivo microfluídico o incluso en una pluralidad de lugares evitando diseñar puertos de entrada y salida para acoplar dispositivos dedicados para la medida o control del caudal. The manufacture of electrodes that are deposited on the outer face of the membrane (1.2) allows sensing and flow control to be placed in any part of the microfluidic device or even in a plurality of places avoiding the design of input and output ports for coupling dedicated devices for the measurement or flow control.
Es también objeto de esta invención la combinación de un dispositivo portátil y del aparato adaptado para operar sobre dicho dispositivo portátil cuando el dispositivo portátil es compatible en su configuración con el aparato de control. The combination of a portable device and the device adapted to operate on said portable device is also object of this invention when the portable device is compatible in its configuration with the control device.
Se ha llevado a cabo al menos un experimento donde se prueba en laboratorio la capacidad de respuesta y de regulación del caudal en un microcanal conforme a la invención. El experimento consiste en establecer sobre el microcanal un flujo determinado por un valor de consigna que sigue una función escalonada creciente. At least one experiment has been carried out where the capacity of response and flow regulation in a microchannel according to the invention is tested in the laboratory. The experiment consists in establishing on the microchannel a flow determined by a setpoint value that follows an increasing step function.
En la figura 8 se muestra en trazo continuo la función creciente según tramos escalonados. La respuesta al caudal se ha medido experimentalmente mediante dos métodos, un primer método que hace uso de la señal obtenida en el termosensor del propio termosensor del dispositivo portátil y un segundo método que hace uso de un caudalímetro comercial dispuesto a la salida del dispositivo portátil incorporado como un dispositivo en serie con la salida del microcanal. Figure 8 shows in continuous line the increasing function according to staggered sections. The response to the flow has been measured experimentally by two methods, a first method that makes use of the signal obtained in the thermosensor of the thermosensor of the portable device itself and a second method that makes use of a commercial flow meter arranged at the output of the built-in portable device how a device in series with the output of the microchannel.
La figura 8 muestra en trazo discontinuo la respuesta obtenida según el primer método y en línea de puntos la respuesta medida mediante el segundo método. Figure 8 shows in broken lines the response obtained according to the first method and in dotted lines the response measured by the second method.
En ambos casos se observa que el caudal se ciñe a la función de consigna con un grado de ajuste alto. Los dos valores de medida difieren dando un grado de inercia algo mayor en la invención posiblemente debido a la barrera térmica que establece la membrana (1.2). No obstante, esta diferencia se ha encontrado aceptable para las aplicaciones a las que está destinada la invención. In both cases it is observed that the flow is limited to the setpoint function with a high degree of adjustment. The two measured values differ giving a somewhat greater degree of inertia in the invention possibly due to the thermal barrier established by the membrane (1.2). However, this difference has been found acceptable for the applications for which the invention is intended.

Claims

REIVINDICACIONES
1. - Un primer producto interrelacionado para el control del caudal en un dispositivo microfluídico, provisto en la forma de un dispositivo portátil (1) que comprende: 1. - A first interrelated product for flow control in a microfluidic device, provided in the form of a portable device (1) comprising:
- una placa soporte (1.1) con al menos un tramo de canal microfluídico (1.4) abierto configurado sobre la superficie de la placa soporte (1.1); - a support plate (1.1) with at least one section of open microfluidic channel (1.4) configured on the surface of the support plate (1.1);
- una primera membrana conductora (1.2) térmicamente unida a la placa soporte (1.1) de tal modo que cubre el al menos un tramo de canal microfluídico (1.4) de tal modo que dicho tramo de canal microfluídico (1.4) queda cerrado por la primera membrana (1.2) conductora;  - a first conductive membrane (1.2) thermally bonded to the support plate (1.1) in such a way that it covers the at least one section of microfluidic channel (1.4) such that said section of microfluidic channel (1.4) is closed by the first conductive membrane (1.2);
- una región en la superficie externa de la primera membrana conductora (1.2), donde el lado opuesto a dicha región está en contacto con al menos parte del tramo del canal microfluídico (1.4), adaptada para recibir un termosensor (1.7.1) de caudal;  - a region on the outer surface of the first conductive membrane (1.2), where the side opposite to said region is in contact with at least part of the section of the microfluidic channel (1.4), adapted to receive a thermosensor (1.7.1) of flow;
- una microválvula (1.6) donde: - a micro valve (1.6) where:
o dicha microválvula (1.6) está configurada según una cavidad (1.6.3) abierta sobre la superficie de la placa soporte (1.1),  or said microvalve (1.6) is configured according to a cavity (1.6.3) open on the surface of the support plate (1.1),
o la cavidad (1.6.3) abierta dispone de una entrada y una salida microfluídicas (1.6.1, 1.6.2),  or the open cavity (1.6.3) has a microfluidic inlet and outlet (1.6.1, 1.6.2),
o la cavidad (1.6.3) abierta está cubierta por una membrana flexible (1.2) de tal modo que dispone de una región de su superficie exterior adaptada para recibir un actuador (3) por presión de tal modo que la presión sobre dicha región provoca la deformación de la membrana flexible (1.2) y el cierre de la microválvula (1.6),  or the open cavity (1.6.3) is covered by a flexible membrane (1.2) in such a way that it has a region of its outer surface adapted to receive an actuator (3) by pressure such that the pressure on said region causes the deformation of the flexible membrane (1.2) and the closure of the microvalve (1.6),
donde o bien la entrada o bien la salida (1.6.1, 1.6.2) de dicha microválvula (1.6) está en conexión fluídica con el tramo de canal microfluídico (1.4). wherein either the inlet or the outlet (1.6.1, 1.6.2) of said microvalve (1.6) is in fluidic connection with the microfluidic channel section (1.4).
2. - Un primer producto de acuerdo a la reivindicación 1, donde el termosensor (1.7.1) de caudal está configurado mediante electrodos (1.7) situados sobre la región de la superficie externa de la primera membrana (1.2) conductora térmicamente. 2. - A first product according to claim 1, wherein the flow thermosensor (1.7.1) is configured by electrodes (1.7) located on the region of the external surface of the first thermally conductive membrane (1.2).
3. - Un primer producto de acuerdo a la reivindicación 2, donde los electrodos (1.7) situados sobre la región de la superficie externa son electrodos depositados mediante "sputtering", evaporación, serigrafía, impresión por chorro o una combinación de cualquiera de ellas. 3. - A first product according to claim 2, wherein the electrodes (1.7) located on the region of the external surface are electrodes deposited by "sputtering", evaporation, screen printing, jet printing or a combination of any of them.
4. - Un primer producto de acuerdo a la reivindicación 1, donde el termosensor (1.7.1) de caudal está configurado mediante una segunda lámina que contiene los electrodos (1.7) que configuran el sensor (1.7.1) sobre una de sus superficies y dicha segunda lámina está fijada sobre la región en la superficie externa de la primera membrana conductora (1.2) adaptada para recibir un termosensor (1.7.1) de caudal de modo que los electrodos (1.7) están en contacto con la primera lámina conductora (1.2) térmicamente. 4. - A first product according to claim 1, wherein the flow thermosensor (1.7.1) is configured by a second sheet containing the electrodes (1.7) that configure the sensor (1.7.1) on one of its surfaces and said second sheet is fixed on the region on the outer surface of the first conductive membrane (1.2) adapted to receive a flow thermosensor (1.7.1) so that the electrodes (1.7) are in contact with the first conductive sheet ( 1.2) thermally.
5. - Un primer producto de acuerdo a la reivindicación 1, donde la primera membrana conductora térmicamente unida a la placa soporte y la membrana flexible que cubre la cavidad abierta de la microválvula es una misma membrana (1.2) flexible y conductora térmicamente. 5. - A first product according to claim 1, wherein the first conductive membrane thermally bonded to the support plate and the flexible membrane covering the open cavity of the microvalve is the same thermally conductive and flexible membrane (1.2).
6. - Un primer producto de acuerdo a la reivindicación 1, donde o bien la entrada o bien la salida (1.6.1, 1.6.2) de dicha microválvula (1.6) parte de la base de su cavidad (1.6.3) abierta, estando dispuesta en oposición a la membrana elástica (1.2) de tal modo que el cierre de la microválvula (1.6) se establece por el apoyo de la membrana (1.2) deformada por la acción del actuador (3) por presión sobre la base de la cavidad (1.6.3) donde está la entrada o salida (1.6.1, 1.6.2). 6. - A first product according to claim 1, wherein either the inlet or the outlet (1.6.1, 1.6.2) of said microvalve (1.6) part of the base of its open cavity (1.6.3) , being arranged in opposition to the elastic membrane (1.2) such that the closure of the microvalve (1.6) is established by the support of the membrane (1.2) deformed by the action of the actuator (3) by pressure on the base of the cavity (1.6.3) where the input or output is (1.6.1, 1.6.2).
7. - Un primer producto de acuerdo a la reivindicación 1, donde la placa soporte (1.1) comprende un microcanal de bypass (1.5) que comunica fluídicamente la entrada al al menos un tramo de canal microfluídico (1.4) abierto configurado sobre la superficie de la placa soporte (1.1) con su salida para el control de un caudal en el dispositivo microfluídico igual al caudal del al menos un tramo de canal microfluídico (1.4) más el caudal del microcanal de bypass. 7. - A first product according to claim 1, wherein the support plate (1.1) comprises a bypass microchannel (1.5) fluidly communicating the input to at least one section of open microfluidic channel (1.4) configured on the surface of the support plate (1.1) with its output for the control of a flow rate in the microfluidic device equal to the flow rate of at least one section of microfluidic channel (1.4) plus the flow rate of the bypass microchannel.
8. - Un primer producto de acuerdo a cualquiera de las reivindicaciones anteriores, donde el dispositivo microfluídico comprende una pluralidad de microválvulas (1.6), cada una de ellas con la entrada adaptada para recibir un fluido, y la pluralidad de salidas de las microválvulas (1.6) en conexión fluídica con la entrada del al menos un tramo de canal microfluídico (1.4) que tiene la región para la medida mediante un termosensor (1.7.1). 8. - A first product according to any of the preceding claims, wherein the microfluidic device comprises a plurality of micro valves (1.6), each with the inlet adapted to receive a fluid, and the plurality of outputs of the micro valves ( 1.6) in fluidic connection with the entrance of the at least one section of microfluidic channel (1.4) that has the region for measurement by means of a thermosensor (1.7.1).
9.- Un primer producto de acuerdo a cualquiera de las reivindicaciones 1 a 7, donde el dispositivo microfluídico comprende: - una pluralidad de tramos de canal microfluídicos (1.4) cada uno de ellos con una región para la medida mediante un termosensor (1.7.1) y una microválvula (1.6);9. A first product according to any of claims 1 to 7, wherein the microfluidic device comprises: - a plurality of microfluidic channel sections (1.4) each with a region for measurement by means of a thermosensor (1.7.1) and a microvalve (1.6);
- una entrada principal de fluido; y, - a main fluid inlet; Y,
donde la entrada principal está en conexión fluídica con la pluralidad tramos de canal microfluídicos (1.4). where the main entrance is in fluidic connection with the plurality of microfluidic channel sections (1.4).
10. - Un primer producto de acuerdo a cualquiera de las reivindicaciones 1 a 7, donde la entrada principal comprende una microválvula principal (1.6) después de la cual se encuentra en conexión fluídica con una pluralidad de tramos de canal microfluídicos (1.4) cada uno de los cuales comprende una región para la medida mediante un termosensor (1.7.1) y una microválvula (1.6). 10. - A first product according to any one of claims 1 to 7, wherein the main inlet comprises a main microvalve (1.6) after which it is in fluidic connection with a plurality of microfluidic channel sections (1.4) each of which it comprises a region for measurement by means of a thermosensor (1.7.1) and a micro valve (1.6).
11. - Un segundo producto interrelacionado para el control del caudal en un dispositivo microfluídico, provisto en la forma de un aparato de control (2) que comprende: 11. - A second interrelated product for flow control in a microfluidic device, provided in the form of a control apparatus (2) comprising:
- un soporte de fijación de un dispositivo portátil (1), - a support for fixing a portable device (1),
- un actuador (3) adaptado para ejercer presión sobre la región de la superficie exterior de la membrana (1.2) flexible situada cubriendo la microválvula (1.6) del dispositivo portátil (1) una vez fijado en el soporte de fijación y que está adaptada para recibir un actuador (3) por presión,  - an actuator (3) adapted to exert pressure on the region of the outer surface of the flexible membrane (1.2) located covering the micro valve (1.6) of the portable device (1) once fixed on the fixing support and which is adapted for receive an actuator (3) by pressure,
- o bien un termosensor (1.7.1) adaptado para entrar en contacto con la región en la superficie externa de la primera membrana (1.2) conductora del dispositivo portátil (1) una vez fijado en el soporte de fijación; o bien, si el dispositivo portátil (1) ya dispone de sensor (1.7.1), medios para entrar en contacto con dicho sensor (1.7.1) cuando el dispositivo portátil (1) está fijado en el soporte de fijación; - or a thermosensor (1.7.1) adapted to come into contact with the region on the outer surface of the first conductive membrane (1.2) of the portable device (1) once fixed on the fixing bracket; or, if the portable device (1) already has a sensor (1.7.1), means for contacting said sensor (1.7.1) when the portable device (1) is fixed on the fixing bracket;
- una unidad central de proceso (CPU): - a central processing unit (CPU):
o que comprende una entrada de señal del termosensor (1.7.1) donde dicha unidad central de proceso (CPU) está adaptada para determinar el caudal que pasa por el al menos un tramo de canal microfluídico (1.4) a partir de la señal de entrada,  or comprising a signal input from the thermosensor (1.7.1) where said central processing unit (CPU) is adapted to determine the flow through the at least one section of microfluidic channel (1.4) from the input signal ,
o que comprende una salida en conexión con el actuador (3) para el control de la microválvula (1.6),  or comprising an outlet in connection with the actuator (3) for the control of the microvalve (1.6),
o que comprende una entrada para establecer un valor de consigna del caudal en el al menos un tramo de canal microfluídico (1.4); y,  or comprising an input to establish a flow setpoint value in the at least one section of microfluidic channel (1.4); Y,
o donde la unidad central de proceso (CPU) está configurada en lazo cerrado para regular el caudal mediante la microválvula (1.6) para alcanzar el valor de consigna. or where the central processing unit (CPU) is configured in closed loop to regulate the flow rate by means of the micro valve (1.6) to reach the value of setpoint.
12. - Un segundo producto según la reivindicación 11, donde: 12. - A second product according to claim 11, wherein:
- el soporte de fijación está adaptado para recibir un dispositivo portátil (1) según la reivindicación 8;  - the fixing support is adapted to receive a portable device (1) according to claim 8;
- comprende tantos actuadores (3) adaptados para ejercer presión como microválvulas (1.6); y,  - It comprises as many actuators (3) adapted to exert pressure as micro valves (1.6); Y,
donde la unidad central de proceso (CPU) comprende una entrada de señal en comunicación con el termosensor (1.7.1) y está adaptada para establecer un lazo cerrado entre el termosensor (1.7.1) y una microválvula (1.6) preestablecida y así mismo el cierre del resto de las microválvulas (1.6). where the central processing unit (CPU) comprises a signal input in communication with the thermosensor (1.7.1) and is adapted to establish a closed loop between the thermosensor (1.7.1) and a preset microvalve (1.6) and likewise the closure of the rest of the microvalves (1.6).
13. - Un segundo producto según la reivindicación 11, donde: 13. - A second product according to claim 11, wherein:
- el soporte de fijación está adaptado para recibir un dispositivo portátil (1) según la reivindicación 9;  - the fixing support is adapted to receive a portable device (1) according to claim 9;
- dispone de tantos actuadores (3) adaptados para ejercer presión como microválvulas (1.6); y,  - it has so many actuators (3) adapted to exert pressure as micro valves (1.6); Y,
donde la unidad central de proceso (CPU) comprende tantas entradas de señal como termosensores (1.7.1) comprende el dispositivo portátil (1) y está adaptada para establecer tantos lazos cerrados entre el termosensor (1.7.1) y la microválvula (1.6) dispuesta en el mismo tramo de canal microfluídico como microválvulas (1.6) comprende el dispositivo portátil (1). where the central processing unit (CPU) comprises as many signal inputs as thermosensors (1.7.1) comprises the portable device (1) and is adapted to establish as many closed loops between the thermosensor (1.7.1) and the microvalve (1.6) arranged in the same section of microfluidic channel as microvalves (1.6) comprises the portable device (1).
14. - Un segundo producto según la reivindicación 11, donde: 14. - A second product according to claim 11, wherein:
- el soporte de fijación está adaptado para recibir un dispositivo portátil (1) según la reivindicación 10;  - the fixing support is adapted to receive a portable device (1) according to claim 10;
- dispone de tantos actuadores (3) adaptados para ejercer presión como microválvulas (1.6), tanto para los tramos de canal microfluídicos (1.4) como para la microválvula (1.6) principal; y,  - it has so many actuators (3) adapted to exert pressure as microvalves (1.6), both for the microfluidic channel sections (1.4) and for the main microvalve (1.6); Y,
donde la unidad central de proceso (CPU) comprende tantas entradas de señal como termosensores (1.7.1) comprende el dispositivo portátil (1) en sus tramos de canal y está adaptada para establecer un lazo cerrado entre un termosensor (1.7.1) determinado y la microválvula (1.6) principal dispuesta en el tramo de canal microfluídico donde se encuentra el termosensor (1.7.1), y así mismo, el cierre del resto de las microválvulas (1.6) situadas en los tramos de canal microfluídicos (1.4). where the central processing unit (CPU) comprises as many signal inputs as thermosensors (1.7.1) comprises the portable device (1) in its channel sections and is adapted to establish a closed loop between a given thermosensor (1.7.1) and the main microvalve (1.6) arranged in the section of the microfluidic channel where the thermosensor (1.7.1) is located, and also, the closure of the rest of the microvalves (1.6) located in the microfluidic channel sections (1.4).
15.- Un sistema que comprende una combinación de un segundo producto interrelacionado (2) de acuerdo a cualquiera de las reivindicaciones 11 a 14 y un primer producto (1) interrelacionado, compatible con el segundo producto (2) interrelacionado, según cualquiera de las reivindicaciones 1 a 10. 15. A system comprising a combination of a second interrelated product (2) according to any of claims 11 to 14 and a first interrelated product (1), compatible with the second interrelated product (2), according to any of the claims 1 to 10.
PCT/ES2013/070746 2013-10-29 2013-10-29 Apparatus for controlling the flow rate in a microfluidic device WO2015063347A1 (en)

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